IL-27, targeting antigen presenting cells, promotes Th17 differentiation and colitis in mice

Th17 cells have been implicated in autoimmunity and inflammatory bowel disease (IBD). Antigen presenting cell (APC) derived cytokines such as IL-1β and IL-6 are key mediators supporting Th17 differentiation, yet how these factors are induced in vivo remains unclear. Here we show that IL-27 acting on APCs enhances IL-6 and IL-1β production and Th17 differentiation. IL-27Rα−/− TCRβ−/− recipients fail to develop gut inflammation following naïve CD4 T cell transfer, while IL-27Rα+/+ TCRβ−/− recipients develop severe colitis. Investigation of T cell responses exhibits that IL-27Rα−/− TCRβ−/− mice do not support Th17 differentiation with significantly decreased levels of IL-6 and IL-1β by APCs. Our study has identified a novel proinflammatory role for IL-27 in vivo that promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs.